Plasma levels of the N-terminal peptide of proopiomelanocortin (NPP) were measured in rainbow trout, Salmo gairdneri, following treatment of handling stress with or without administration of dexamethasone, adaptation to white and black background, and maintenance on a constant light/dark cycle. Effects of exogenously administered NPP on plasma constituents were also examined to provide insight into the biological significance of NPP. Thirty minutes of handling stress in shallow water had no effect on plasma levels of NPP during and after the stress period, whereas significant increases in plasma cortisol and glucose were observed. Intraperitoneal administration of dexamethasone blocked the stress-induced elevation of plasma levels of cortisol and caused a depression of plasma NPP. No difference was observed in plasma levels of NPP between trout adapted to a white background and those adapted to a black background. No diurnal changes in NPP were observed under an artificial light/dark cycle (14L/10D light cycle, 0500-1900 hr light) in May and September. Thus, plasma levels of NPP were considerably constant under various physiological conditions, and no synchronism was observed between plasma NPP and cortisol, although NPP modifies the corticotropin-induced release of cortisol from the interrenal. Plasma constituents such as cortisol, total protein, albumin, plasma amino nitrogen, glucose, free fatty acid, ketone body, sodium, potassium, calcium, and magnesium were not altered by intraperitoneal injections of NPP (1 or 10 micrograms) once daily for 6 days (total of six injections) or once every other day for 28 days (14 injections). High concentrations of NPP were found in the plasma 24 hr after cessation of the serial injections of NPP (10 micrograms), suggesting slow metabolic clearance of the peptide.